{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T19:39:57Z","timestamp":1790105997813,"version":"4.0.1"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Autophagy can either support cell survival or promote cell death in response to therapeutic stress, yet the molecular switch that determines this directionality remains poorly defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using kaempferol as a proof\u2011of\u2011concept flavonoid and esophageal squamous carcinoma cells as a model system, we investigated its dose\u2011dependent effects on the HSP70\u2013Beclin\u20111 complex.\n                      <jats:italic>In vivo<\/jats:italic>\n                      experiments were also performed to evaluate kaempferol\u2019s modulation of cisplatin\u2019s antitumor activity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Low\u2011dose kaempferol stabilized the HSP70\u2013Beclin\u20111 association, suppressed autophagic flux, and attenuated chemotherapy\u2011induced apoptosis. In contrast, high\u2011dose kaempferol disrupted this complex and enhanced autophagic flux through coordinated activation of AMPK\/mTOR inhibition and ER stress\u2013JNK signaling, leading to robust autophagy\u2011dependent chemosensitization. In vivo, high\u2011dose kaempferol potentiated cisplatin\u2019s antitumor activity, whereas low\u2011dose kaempferol diminished it.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings reveal a generalizable molecular logic in which dose\u2011dependent modulation of a chaperone\u2013autophagy initiation complex governs autophagy directionality and therapeutic response. By elucidating how a single compound can toggle this central regulatory node, the study provides a conceptual framework for optimizing the dosing of natural products and for leveraging autophagy\u2011based chemosensitization strategies across diverse tumor contexts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1802609","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T05:44:57Z","timestamp":1779255897000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Dose-dependent tuning of HSP70\u2013Beclin-1 by kaempferol governs autophagy and chemosensitivity"],"prefix":"10.3389","volume":"16","author":[{"given":"Suqin","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary Spleen and Stomach, Henan Province Hospital of Traditional Chinese Medicine","place":["Zhengzhou, 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Province Hospital of Traditional Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihuan","family":"Yan","sequence":"additional","affiliation":[{"name":"Second Clinical Medical College, Henan University of Traditional Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Second Clinical Medical College, Henan University of Traditional Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Henan Provincial People\u2019s Hospital","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinsheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary 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